Diallylamine → Sonolisib

HRID 2240568Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2240568
[CH3:1][C:2]([O:4][C@H:5]1[C:14]2[C@@:15]3([CH3:30])[C@@H:26]([CH2:27][O:28][CH3:29])[O:25][C:23](=[O:24])[C:17]4=[CH:18][O:19][C:20]([C:21](=[O:22])[C:13]=2[C@@H:8]2[CH2:9][CH2:10][C:11](=[O:12])[C@@:7]2([CH3:31])[CH2:6]1)=[C:16]34)=[O:3].[CH2:32]([NH:35][CH2:36][CH:37]=[CH2:38])[CH:33]=[CH2:34]>C(Cl)Cl>[CH3:1][C:2]([O:4][C@H:5]1[C:14]2[C@:15]3([CH3:30])[C:16](=[C:20]([OH:19])[C:21](=[O:22])[C:13]=2[C@@H:8]2[CH2:9][CH2:10][C:11](=[O:12])[C@@:7]2([CH3:31])[CH2:6]1)/[C:17](=[CH:18]\[N:35]([CH2:36][CH:37]=[CH2:38])[CH2:32][CH:33]=[CH2:34])/[C:23](=[O:24])[O:25][C@@H:26]3[CH2:27][O:28][CH3:29])=[O:3]

Komponenten

4

Edukt 2

HCID 31279DiallylamineHCID 312145Wortmannin

Produkt 1

HCID 9849735SonolisibAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of wortmannin (10.7 mg, 25.0 μmol) in CH2Cl2 (125 μL) was added a freshly prepared 0.2 M stock solution of diallylamine (138 μL, 27.5 μmol) in CH2Cl2. The reaction mixture was stirred at room temperature for 1 h. The solvent and excess amine were removed in vacuo, and the product was purified via chromatography on SiO2 (hexanes/ethyl acetate, 1:9) to give PX-866 (9.0 mg, 17 μmol, 68%) as an orange oil. The product was analyzed by several experimental methods and shown to be of the correct structure and of high purity as: [α]D −630 (c 0.0015, CH2Cl2, 23° C.); IR (KBr) 3391, 1743, 1695, 1685, 1622, 1569, 1222, 1111, 1100 cm−1; 1H NMR δ 8.20 (s, 1H), 6.81 (s, 1H), 6.06 (dd, 1H, J=7.4, 4.8 Hz), 5.85 (br s, 1H), 5.62 (br, 1H), 5.44-5.04 (m, 4H), 4.48 (dd, 1H, J=7.2, 1.9 Hz), 4.05-3.60 (m, 4H), 3.26 (s, 3H), 3.27-3.20 (m, 1H), 3.16 (dd, 1H, J=10.9, 7.2 Hz), 3.00-2.90 (m, 2H), 2.59 (dd, 1H, J=19.4, 8.6 Hz), 2.40 (dd, 1H, J=14.4, 7.7 Hz), 2.35-2.07 (m, 2H), 2.07 (s, 3H), 1.83 (dd, 1H, J=14.4, 4.7 Hz), 1.54 (s, 3H), 0.86 (s, 3H); 13C NMR δ 217.0, 178.5, 169.6, 164.8, 156.3, 151.5, 139.0, 136.9, 132.2, 131.3, 127.7 (2 C), 119.2, 89.0, 81.9, 73.1, 67.6, 59.1, 50.9 (2 C), 48.9, 42.3, 42.2, 37.5, 36.0, 24.6, 22.2, 20.8, 16.1; MS (EI) m/z (rel. intensity) 525 (M′, 11), 466 (17), 391 (15), 350 (14), 323 (13), 266 (17), 239 (17), 60 (100); HRMS (EI) calculated for C29H35NO8 525.2363; found 525.2386.

Aufarbeitung

  1. customThe solvent and excess amine were removed in vacuo
  2. customthe product was purified via chromatography on SiO2 (hexanes/ethyl acetate, 1:9)

Quellen und Nachweise

ORD-Eintrag
ord-e38a3279fca04915869a816b51cef3a5
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07723375B2

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